Mammalian cells dynamically interact with the surrounding microenvironments through cell surface molecules. This dynamic interaction is crucial in many processes from wound healing, immune cell infiltration to cancer invasion. Two important classes of cell surface receptors that mediate cell-matrix and cell-cell adhesions are integrins and cadherins, respectively. They are assembled into large adhesion complexes (integrin-based focal adhesions and cadherin-based adherens junctions) and via actin-binding proteins play an important role in mechanical coupling the cell to other cells as well to the extracellular matrix (ECM). Besides providing an important structural basis for anchoring the actin cytoskeleton to the plasma membrane, these adhesive structures can also influence signaling events that control important cellular processes, such as cell survival, proliferation and differentiation. Genetic defects in critical components of the cell adhesion junctions are part of various rare diseases. Altered signaling in cancer can contribute to increased dynamics of focal adhesions and/or adherens junctions, and promote the motile phenotype of cancer cells that drives cancer metastasis. Finally, chemotactic signaling is the driving force for immune cell migration and hence critical in inflammatory processes that mediate cancer and other diseases.
Subjects covered by the course:
In this course Cell adhesion signaling in health and disease, prominent Dutch scientists will discuss the latest advances concerning the function and structure of the above mentioned two classes of cell adhesion receptors. Subjects that will be covered are (1) how cells sense, via their adhesion junctions, their physical microenvironment and respond with appropriate mechanosignaling events that regulate gene expression and differentiation, (2) how the mechanical signals of adhesion receptors are integrated with those originating from growth factor receptors to support cell proliferation and survival, (3) how dynamic remodeling of the actin cytoskeleton and trafficking of adhesion receptors contribute to cell migration and tumor invasion, (4) how we can elucidate and safely apply novel therapeutic approaches to interfere with cell adhesion and thereby prevent, cure or inhibit progression of different diseases.
Dr. Arnoud Sonnenberg
Adequate knowledge of Cell Biology, Biochemistry and Genetics.
Minimum of 5 students, maximum of 25 students.
Mode of instruction
Lectures, literature review and discussions.
Will be announced during the course.
The aim of the course is to understand at the molecular level 1) how cells communicate through cell-cell and cell-matrix interactions with their environment and 2) how the local extracellular environment regulates several aspects of cell behavior, e.g. cell proliferation, survival and migration through these interactions. A deeper molecular and mechanistic understanding of the regulation of these interactions as well as defects in the circuitry that regulates these interactions in disease states is essential for future therapeutic applications.
Participation in discussion groups, presentation, literature report, and an essay exam.
The lecture series “Cell adhesion signaling in health and disease” is usually taught in May / June.
Application via uSis. Registration closes 1 month before the start of the course.
A minimum of 5 students and a maximum of 25 students applies to this course.